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. 1997 Oct 15;100(8):2079–2084. doi: 10.1172/JCI119741

A synthetic peptide derived from the sequence of a type I collagen receptor inhibits type I collagen-mediated platelet aggregation.

T M Chiang 1, A H Kang 1
PMCID: PMC508399  PMID: 9329973

Abstract

A synthetic peptide-1, an 18 amino acid residue peptide derived from a hydrophilic domain of a cloned platelet type I collagen receptor, was used to study the role of the receptor on types I and III collagen-induced platelet aggregation and the release of ATP. The peptide inhibits the type I, but not the type III, collagen-induced platelet aggregation and the release of ATP in a dose-dependent manner. The [125I]peptide-1 specifically binds to type I collagen-coated microtiter wells in a dose-dependent manner (with Kd = 10 nM). The binding of [125I]peptide-1 can be inhibited by an excess of unlabeled peptide-1 suggesting that the binding is specific. The labeled peptide-1 does not bind to type III collagen-coated microtiter wells. Results from an enzyme-linked immunosorbent assay show that the peptide reacts with the poly- and monoclonal antibodies raised against the purified platelet type I collagen receptor (Mr 65 kD). The peptide also inhibits the adhesion of platelets on type I collagen matrix and rabbit aortic segments in a dose-dependent manner. These results suggest that the reactive site of the platelet receptor for type I collagen resides in this portion of the molecule.

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Selected References

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  1. BORN G. V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962 Jun 9;194:927–929. doi: 10.1038/194927b0. [DOI] [PubMed] [Google Scholar]
  2. Barber A. J., Jamieson G. A. Isolation and characterization of plasma membranes from human blood platelets. J Biol Chem. 1970 Dec 10;245(23):6357–6365. [PubMed] [Google Scholar]
  3. Chiang T. M., Beachey E. H., Kang A. H. Interaction of a chick skin collagen fragment (alpha1-CB5) with human platelets. Biochemical studies during the aggregation and release reaction. J Biol Chem. 1975 Sep 10;250(17):6916–6922. [PubMed] [Google Scholar]
  4. Chiang T. M., Jin A., Kang A. H. Platelet-collagen interaction. Inhibition by a monoclonal antibody raised against collagen receptor. J Immunol. 1987 Aug 1;139(3):887–892. [PubMed] [Google Scholar]
  5. Chiang T. M., Kang A. H., Dale J. B., Beachey E. H. Immunochemical studies of the purified human platelet receptor for the alpha 1(I)-chain of chick skin collagen. J Immunol. 1984 Aug;133(2):872–876. [PubMed] [Google Scholar]
  6. Chiang T. M., Kang A. H. Isolation and purification of collagen alpha 1(I) receptor from human platelet membrane. J Biol Chem. 1982 Jul 10;257(13):7581–7586. [PubMed] [Google Scholar]
  7. Chiang T. M., Rinaldy A., Kang A. H. Cloning, characterization, and functional studies of a nonintegrin platelet receptor for type I collagen. J Clin Invest. 1997 Aug 1;100(3):514–521. doi: 10.1172/JCI119560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chiang T. M., Seyer J. M., Kang A. H. Collagen-platelet interaction: separate receptor sites for types I and III collagen. Thromb Res. 1993 Sep 15;71(6):443–456. doi: 10.1016/0049-3848(93)90118-8. [DOI] [PubMed] [Google Scholar]
  9. Davis G. E. Affinity of integrins for damaged extracellular matrix: alpha v beta 3 binds to denatured collagen type I through RGD sites. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1025–1031. doi: 10.1016/0006-291x(92)91834-d. [DOI] [PubMed] [Google Scholar]
  10. Deckmyn H., Van Houtte E., Vermylen J. Disturbed platelet aggregation to collagen associated with an antibody against an 85- to 90-Kd platelet glycoprotein in a patient with prolonged bleeding time. Blood. 1992 Mar 15;79(6):1466–1471. [PubMed] [Google Scholar]
  11. Gartner T. K., Bennett J. S. The tetrapeptide analogue of the cell attachment site of fibronectin inhibits platelet aggregation and fibrinogen binding to activated platelets. J Biol Chem. 1985 Oct 5;260(22):11891–11894. [PubMed] [Google Scholar]
  12. Kotite N. J., Staros J. V., Cunningham L. W. Interaction of specific platelet membrane proteins with collagen: evidence from chemical cross-linking. Biochemistry. 1984 Jun 19;23(13):3099–3104. doi: 10.1021/bi00308a038. [DOI] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Moroi M., Jung S. M., Okuma M., Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion. J Clin Invest. 1989 Nov;84(5):1440–1445. doi: 10.1172/JCI114318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  16. Santoro S. A., Zutter M. M., Wu J. E., Staatz W. D., Saelman E. U., Keely P. J. Analysis of collagen receptors. Methods Enzymol. 1994;245:147–183. doi: 10.1016/0076-6879(94)45010-2. [DOI] [PubMed] [Google Scholar]
  17. Seyer J. M., Kang A. H. Covalent structure of collagen: amino acid sequence of alpha 1(III)-CB9 from type III collagen of human liver. Biochemistry. 1981 Apr 28;20(9):2621–2627. doi: 10.1021/bi00512a040. [DOI] [PubMed] [Google Scholar]
  18. Seyer J. M., Mainardi C., Kang A. H. Covalent structure of collagen: amino acid sequence of alpha 1 (III)-CB5 from type III collagen of human liver. Biochemistry. 1980 Apr 15;19(8):1583–1589. doi: 10.1021/bi00549a008. [DOI] [PubMed] [Google Scholar]
  19. Staatz W. D., Fok K. F., Zutter M. M., Adams S. P., Rodriguez B. A., Santoro S. A. Identification of a tetrapeptide recognition sequence for the alpha 2 beta 1 integrin in collagen. J Biol Chem. 1991 Apr 25;266(12):7363–7367. [PubMed] [Google Scholar]
  20. Staatz W. D., Walsh J. J., Pexton T., Santoro S. A. The alpha 2 beta 1 integrin cell surface collagen receptor binds to the alpha 1 (I)-CB3 peptide of collagen. J Biol Chem. 1990 Mar 25;265(9):4778–4781. [PubMed] [Google Scholar]
  21. Tandon N. N., Kralisz U., Jamieson G. A. Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion. J Biol Chem. 1989 May 5;264(13):7576–7583. [PubMed] [Google Scholar]
  22. Yamada K. M. Adhesive recognition sequences. J Biol Chem. 1991 Jul 15;266(20):12809–12812. [PubMed] [Google Scholar]

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